This is the second resubmission of an application for a Midcareer Investigator Award in Patient-Oriented Research (K24) in response to PA-00-005 focused in the areas of Child Psychiatry/Pediatric Psychopharmacology and Addictive Disorders. The overall objectives of the applicant are to a) increase the candidate's knowledge in completing clinical trials in adolescents with substance use disorders (SUD, including drug or alcohol abuse or dependence), b) heighten his involvement in training and mentoring, and 3) complete a five year prospective study of the efficacy of atomoxetine (ATMX) in the treatment of adolescents with Attention- Deficit/Hyperactivity Disorder (ADHD) plus SUD. This Award would also provide an opportunity to develop a well-integrated Center for the diagnosis and treatment of adolescent SUD integrated seamlessly into the pediatric psychopharmacology clinic at the Massachusetts General Hospital (MGH). Substance use disorders constitute one of the most feared outcomes and difficult to manage clinical problems in adolescents with ADHD. High rates of ADHD have been reported in adolescents with SUD. Conversely, untreated ADHD is a risk factor for the development of SUD. Despite this bi-directional overlap, little data are available to guide clinicians in the treatment of ADHD plus SUD in adolescents. ATMX, a recently approved norepinephrine reuptake inhibitor, has been shown to be effective in the treatment of ADHD; however, ATMX remains untested in individuals with SUD. The aim of this research proposal is to evaluate prospectively the efficacy of ATMX in adolescents with ADHD plus SUD. We plan to evaluate systematically adolescents with ADHD plus SUD, treat all of these adolescents with six courses of cognitive behavioral therapy, and randomize youth equally to receive ATMX or placebo. We will evaluate outcome in multiple domains including ADHD, SUD, other psychopathology, and safety parameters throughout the twelve-week trial. In this way, we will follow current clinical guidelines of addressing the SUD prior to ADHD; while accruing valuable information as to the efficacy of a novel non-stimulant medication in treating ADHD, as well as the effects on SUD and functional outcome. This investigation will provide the research template for the five-year award providing an excellent foundation for the applicant to further his own knowledge. Through offsite collaborative efforts, the candidate plans to develop specific skills related to the integration of psycho-social (particularly cognitive-behavioral therapy) and psychopharmacological trials in adolescent SUD trials, and methodological and conceptual issues in the testing of compounds for SUD in adolescents with SUD. The Award would also provide the opportunity for the candidate to expand roles in mentoring residents, Child Psychiatry Fellows, and junior faculty on complementary methodology within Child Psychiatry/Pediatric psychopharmacology and the Addictions. Through didactic seminars, supervision, individual and group meetings, and involvement in ongoing research studies - including the proposed research project - the applicant proposes to systematically mentor individuals at all levels of their training and professional careers in the overlap fields of Child Psychiatry/Pediatric Psychopharmacology and SUD. It is anticipated that trainees will develop skills necessary to further develop their careers independently, thus providing future researchers in a vastly underrepresented area in the fields of Child Psychiatry and Addictions. In this manner, the candidate will satisfy overall career development and mentoring objectives of the K24 award.